PRKCA

Summary

PRKCA (protein kinase C alpha, HGNC:9393) is a protein-coding gene on chromosome 17q24.2, encoding Protein kinase C alpha type (P17252). Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, p….

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes.

Source: NCBI Gene 5578 — RefSeq curated summary.

At a glance

• GWAS associations: 53
• Clinical variants (ClinVar): 70 total
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9393
Approved symbol	PRKCA
Name	protein kinase C alpha
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	PKCα
Ensembl gene	ENSG00000154229
Ensembl biotype	protein_coding
OMIM	176960
Entrez	5578

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000284384, ENST00000413366, ENST00000578063, ENST00000583361, ENST00000583775, ENST00000882063, ENST00000960436

RefSeq mRNA: 1 — MANE Select: NM_002737 NM_002737

CCDS: CCDS11664

Canonical transcript exons

ENST00000413366 — 17 exons

Exon	Start	End
ENSE00001612310	66302613	66303024
ENSE00001702669	66803873	66810743
ENSE00001780350	66496201	66496283
ENSE00002270455	66773987	66774067
ENSE00002274391	66786867	66786974
ENSE00002296167	66788839	66788979
ENSE00003470601	66742622	66742760
ENSE00003489361	66306096	66306127
ENSE00003490584	66687111	66687267
ENSE00003513026	66688302	66688436
ENSE00003541546	66645383	66645511
ENSE00003545384	66732688	66732825
ENSE00003551970	66688951	66689047
ENSE00003560317	66738764	66738855
ENSE00003573265	66735489	66735662
ENSE00003597909	66741659	66741721
ENSE00003647566	66641355	66641466

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.5043 / max 577.2568, expressed in 1777 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162296	24.5373	1746
162295	1.8833	1043
162317	1.5953	633
162294	0.7486	391
162314	0.2259	5
162292	0.1967	77
162293	0.1957	69
162316	0.1215	46

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	99.21	gold quality
lateral globus pallidus	UBERON:0002476	98.81	gold quality
trigeminal ganglion	UBERON:0001675	98.33	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.87	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.86	gold quality
entorhinal cortex	UBERON:0002728	97.83	gold quality
postcentral gyrus	UBERON:0002581	97.76	gold quality
parietal lobe	UBERON:0001872	97.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.54	gold quality
substantia nigra pars compacta	UBERON:0001965	97.25	gold quality
inferior olivary complex	UBERON:0002127	97.21	gold quality
endothelial cell	CL:0000115	97.12	gold quality
medulla oblongata	UBERON:0001896	97.02	gold quality
ventral tegmental area	UBERON:0002691	97.02	gold quality
dorsal root ganglion	UBERON:0000044	96.90	gold quality
subthalamic nucleus	UBERON:0001906	96.90	gold quality
choroid plexus epithelium	UBERON:0003911	96.75	gold quality
middle temporal gyrus	UBERON:0002771	96.53	gold quality
cranial nerve II	UBERON:0000941	96.50	gold quality
superior vestibular nucleus	UBERON:0007227	96.50	gold quality
olfactory bulb	UBERON:0002264	96.35	gold quality
orbitofrontal cortex	UBERON:0004167	96.34	gold quality
superior frontal gyrus	UBERON:0002661	96.33	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.99	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.83	gold quality
inferior vagus X ganglion	UBERON:0005363	95.27	gold quality
occipital lobe	UBERON:0002021	94.72	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.62	gold quality
globus pallidus	UBERON:0001875	94.43	gold quality
seminal vesicle	UBERON:0000998	94.18	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1173.79
E-HCAD-35	yes	75.02
E-CURD-119	yes	30.00
E-HCAD-25	yes	19.79
E-ANND-3	yes	9.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, EGR1, ELK1, ESR1, IRF2, IRF3, IRF6, JUN, MZF1, NFKB, RARA, RARB, SP1, TFAP2A, TP53

miRNA regulators (miRDB)

353 targeting PRKCA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976

Literature-anchored findings (GeneRIF, showing 40)

• activation required for vitamin C-succinate induced apoptosis of HL-60 cells (PMID:11688977)
• Four residues located near the calcium binding site of PKC alpha are critical for activation and in vivo membrane translocation of the enzyme. (PMID:11705379)
• Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors (PMID:11740573)
• PKCalpha is required for ET-1-induced human myometrial cell growth (PMID:11751262)
• the first report of focal adhesion kinase and phosphatidylinositol 3-kinase-dependent PKC-alpha activation in bacterial invasion related to cytoskeletal reorganization (PMID:11805101)
• role in induction of metallproteinases 1 and 3 in fibroblasts by basic calcium phosphate crystals (PMID:11836255)
• Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. (PMID:11864971)
• PKC alpha expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox. (PMID:12056906)
• Data show that protein kinase Calpha mediates the effect of antiarrhythmic peptide on gap junction conductance. (PMID:12064599)
• REVIEW:Interaction of protein kinase C isozymes with membranes containing anionic phospholipids utilizing fluorescent phorbol esters to probe the properties of the C1 domains (PMID:12093536)
• PKC alpha functions as a negative modulator of calcineurin-regulated retinoid X receptor responsive element-dependent transcription during T cell activation. (PMID:12097375)
• A294G mutation of protein kinase C alpha does not detectably affect its biochemical properties in vitro or in vivo, and is at least rare in thyroid neoplasias (PMID:12173071)
• Cis activation of the basal promoter of the PKC alpha gene occurs through an activator protein-2-dependent, phorbol ester-responsive pathway, which suggests an autoregulatory manner of transcription in glioblastoma multiforme cells. (PMID:12269829)
• Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. (PMID:12351446)
• Protein kinase C alpha plays an important role in activating store-operated Ca2+ channels (SOC) in human mesangial cells (PMID:12372800)
• Activation of PKCalpha stabilizes F-actin and thereby opposes the effect of PKCepsilon on membrane remodeling in T84 cells. (PMID:12372816)
• Our findings present original data that PKCalpha is the isoform specifically involved in the proliferation of primary human osteoblasts. (PMID:12412804)
• greater increase of PKCalpha translocation after PMA treatment in breast cancer erythrocytes compared to controls was observed (PMID:12490289)
• Il-2 increased protein kinase C alpha expression, but polysaccharide K decreased it. (PMID:12536241)
• the direct PKC-dependent activation of the amyloid protein precursor secretory pathway is compromised by reduced PKCalpha expression and a specific role of this isoform in these mechanisms (PMID:12610653)
• PKCalpha may regulate Ets1 activity in invasive breast cancer cells (PMID:12632071)
• PKC alpha plays a necessary role in mediating calcium-induced differentiation. Failure to regulate PKC alpha in SCC4 carcinoma cells may underlie at least part of the failure of calcium to promote differentiation in these cells. (PMID:12652652)
• Filamin A was identified as a direct binding partner of protein kinase Calpha; two binding sites were identified on filamin A; a Ca2+ and phospholipid-dependent association of the regulatory domain of protein kinase C with these sites was revealed. (PMID:12704190)
• PKCalpha is involved in the regulation of Ca2+-induced platelet aggregation. (PMID:12724315)
• data demonstrate a pathway of Rho activation involving protein kinase c alpha-dependent phosphorylation of p115Rho guanine exchange factor (PMID:12754211)
• The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression (PMID:12783114)
• Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway (PMID:12824193)
• protein kinase C alpha associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells, which contributes to the cell’s high invasive potential. (PMID:12839565)
• Protein kinase C alpha negatively regulates cell spreading and motility in breast cancer cells. (PMID:12878187)
• PKC alpha phosphorylates diacylglycerol kinase zeta in cells, and this phosphorylation inhibits its kinase activity to remove cellular diacylglycerol, thereby affecting cell growth. (PMID:12890670)
• Loss of protein kinase Calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma. (PMID:12907651)
• protein kinase C alpha signaling is activated by apolipoprotein A-I, and it has a role in phosphorylation and stabilization of ATP binding cassette transporter A1 for the high density lipoprotein assembly (PMID:12952980)
• the affinity of isolated C1A and C1B domains of PKCalpha and PKCgamma for soluble and membrane-incorporated DAG and phorbol ester were measured by isothermal calorimetry and surface plasmon resonance in order to compare activation mechanisms (PMID:12954613)
• there is an impairment of degradation of protein kinase c alpha in huntington disease 150q cells that is connected with the sequestration of proteasome on mutant huntingtin aggregates (PMID:12960759)
• PKCA acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T-lymphocytes. (PMID:12972622)
• PKCalpha and betaII have roles in the regulation of membrane recycling (PMID:14527960)
• in gastric cancer, protein translocation of PLCgamma2 and PKCalpha is critical event in the process of apoptosis induction. (PMID:14606067)
• PKC-alpha and PKC-epsilon act cooperatively in regulating JNK activation in response to PMA (PMID:14709334)
• Only PKC-alpha is involved in the signal transduction cascade leading to neutrophil transepithelial migration. (PMID:14739142)
• PKC alpha is a critical regulatory element that is required for efficient regulatory volume decrease in HeLa cells (PMID:14960580)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcab	ENSDARG00000099841
danio_rerio	prkcaa	ENSDARG00000115657
mus_musculus	Prkca	ENSMUSG00000050965
rattus_norvegicus	Prkca	ENSRNOG00000003491
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PKN3 (ENSG00000160447), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Protein kinase C alpha type — P17252 (reviewed: P17252)

All UniProt accessions (4): P17252, J3KN97, J3KRN5, L7RSM7

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at ‘Ser-52’ facilitating its ubiquitination and proteasomal degradation. Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4. Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Subunit / interactions. Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1. Interacts with ADAP1/CENTA1. Interacts with CSPG4. Binds to CAVIN2 in the presence of phosphatidylserine. Interacts with PRKCABP/PICK1 (via PDZ domain). Interacts with TRIM41. Interacts with PARD3. Interacts with SOCS2.

Subcellular location. Cytoplasm. Cell membrane. Mitochondrion membrane. Nucleus.

Post-translational modifications. In response to growth factors, phosphorylated at Thr-631 and Ser-657 by the mTORC2 complex, promoting autophosphorylation and activation of PRKCA.

Activity regulation. Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.

Cofactor. Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

RefSeq proteins (1): NP_002728* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014375	Protein_kinase_C_a/b/g	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR020454	DAG/PE-bd	Domain
IPR034663	cPKC_alpha	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00069, PF00130, PF00168, PF00433

Enzyme classification (BRENDA):

• EC 2.7.11.13 — protein kinase C (BRENDA: 25 organisms, 203 substrates, 258 inhibitors, 20 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FKKQGSFAKKK	0.0166–0.0599	10
ATP	0.0001–0.0828	4
N6-PHENYL-ATP	0.0124	1
S6-(229-239) PEPTIDE	0.0036	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (89 total): strand 22, helix 20, binding site 17, modified residue 14, sequence variant 4, domain 3, turn 2, zinc finger region 2, initiator methionine 1, chain 1, mutagenesis site 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4DNL	X-RAY DIFFRACTION	1.9
8U37	X-RAY DIFFRACTION	2.48
4RA4	X-RAY DIFFRACTION	2.63
3IW4	X-RAY DIFFRACTION	2.8
8UAK	X-RAY DIFFRACTION	2.82
2ELI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17252-F1	86.90	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 463 (proton acceptor)

Ligand- & substrate-binding residues (17): 187; 193; 195; 245; 246; 246; 247; 248; 248; 248; 252; 254 …

Post-translational modifications (14): 2, 10, 226, 319, 494, 495, 497, 501, 628, 631, 638, 651, 657, 658

Mutagenesis-validated functional residues (1):

Position	Phenotype
368	abolished protein kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

69 pathways

ID	Pathway
R-HSA-111933	Calmodulin induced events
R-HSA-114516	Disinhibition of SNARE formation
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1433559	Regulation of KIT signaling
R-HSA-2179392	EGFR Transactivation by Gastrin
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-3000170	Syndecan interactions
R-HSA-399997	Acetylcholine regulates insulin secretion
R-HSA-4086398	Ca2+ pathway
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors
R-HSA-418597	G alpha (z) signalling events
R-HSA-4419969	Depolymerization of the Nuclear Lamina
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5218921	VEGFR2 mediated cell proliferation
R-HSA-5668599	RHO GTPases Activate NADPH Oxidases
R-HSA-76005	Response to elevated platelet cytosolic Ca2+
R-HSA-8853659	RET signaling
R-HSA-9010642	ROBO receptors bind AKAP5
R-HSA-109582	Hemostasis
R-HSA-111885	Opioid Signalling
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1227986	Signaling by ERBB2

MSigDB gene sets: 856 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_COGNITION, BIOCARTA_TEL_PATHWAY, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_RESPONSE_TO_ESTRADIOL, BIOCARTA_EDG1_PATHWAY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_SYNAPSE_ASSEMBLY, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID

GO Biological Process (53): response to reactive oxygen species (GO:0000302), angiogenesis (GO:0001525), positive regulation of endothelial cell proliferation (GO:0001938), desmosome assembly (GO:0002159), protein phosphorylation (GO:0006468), mitotic nuclear membrane disassembly (GO:0007077), cell adhesion (GO:0007155), learning or memory (GO:0007611), response to mechanical stimulus (GO:0009612), response to toxic substance (GO:0009636), positive regulation of endothelial cell migration (GO:0010595), positive regulation of cardiac muscle hypertrophy (GO:0010613), negative regulation of translation (GO:0017148), central nervous system neuron axonogenesis (GO:0021955), positive regulation of cell migration (GO:0030335), positive regulation of lipopolysaccharide-mediated signaling pathway (GO:0031666), positive regulation of insulin secretion (GO:0032024), response to estradiol (GO:0032355), negative regulation of glial cell apoptotic process (GO:0034351), intracellular signal transduction (GO:0035556), response to peptide hormone (GO:0043434), regulation of mRNA stability (GO:0043488), positive regulation of blood vessel endothelial cell migration (GO:0043536), response to ethanol (GO:0045471), positive regulation of macrophage differentiation (GO:0045651), positive regulation of angiogenesis (GO:0045766), positive regulation of bone resorption (GO:0045780), positive regulation of cell adhesion (GO:0045785), positive regulation of exocytosis (GO:0045921), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of smooth muscle cell proliferation (GO:0048661), response to corticosterone (GO:0051412), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of synapse assembly (GO:0051965), positive regulation of ERK1 and ERK2 cascade (GO:0070374), protein kinase C signaling (GO:0070528), response to interleukin-1 (GO:0070555), regulation of platelet aggregation (GO:0090330), apoptotic signaling pathway (GO:0097190), positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0106071)

GO Molecular Function (17): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), calcium,diacylglycerol-dependent serine/threonine kinase activity (GO:0004698), integrin binding (GO:0005178), ATP binding (GO:0005524), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), diacylglycerol binding (GO:0019992), histone H3T6 kinase activity (GO:0035403), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), signaling receptor binding (GO:0005102), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), mitochondrial membrane (GO:0031966), alphav-beta3 integrin-PKCalpha complex (GO:0035866), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), nucleus (GO:0005634), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-20 pathways:

Category	Pathways
CaM pathway	1
Response to elevated platelet cytosolic Ca2+	1
Signaling by ERBB2	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by SCF-KIT	1
Gastrin-CREB signalling pathway via PKC and MAPK	1
The phototransduction cascade	1
Non-integrin membrane-ECM interactions	1
Regulation of insulin secretion	1
Beta-catenin independent WNT signaling	1
Trafficking of AMPA receptors	1
GPCR downstream signalling	1
Nuclear Envelope Breakdown	1
Regulation of mRNA stability by proteins that bind AU-rich elements	1
PCP/CE pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
intracellular membrane-bounded organelle	3
response to oxygen-containing compound	2
intracellular anatomical structure	2
protein kinase activity	2
protein serine/threonine kinase activity	2
protein binding	2
response to oxidative stress	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
desmosome organization	1
cell-cell junction assembly	1
phosphorylation	1
protein modification process	1
mitotic cell cycle	1
nuclear membrane disassembly	1
mitotic cell cycle process	1
cellular process	1
behavior	1
cognition	1
response to external stimulus	1
response to abiotic stimulus	1
response to chemical	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
axonogenesis	1
central nervous system neuron development	1
cell migration	1

Protein interactions and networks

STRING

3696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKCA	PICK1	Q9NRD5	993
PRKCA	SDC4	P31431	973
PRKCA	RACK1	P25388	959
PRKCA	DLG4	P78352	939
PRKCA	CAV1	Q03135	876
PRKCA	SRC	P12931	866
PRKCA	CDC42	P21181	801
PRKCA	RICTOR	Q6R327	784
PRKCA	ADCY8	P40145	754
PRKCA	RHO	P08100	751
PRKCA	PPARG	P37231	733
PRKCA	PKP2	Q99959	728
PRKCA	CALM1	P02593	726
PRKCA	RHOA	P06749	726
PRKCA	ACTN4	O43707	723

IntAct

437 interactions, top by confidence:

A	B	Type	Score
PRKCA	LIPT1	psi-mi:“MI:0915”(physical association)	0.670
EGFR	PRKCA	psi-mi:“MI:0915”(physical association)	0.630
APLP2	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	BAGE	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	CPN1	psi-mi:“MI:0915”(physical association)	0.560
CTSO	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	DRD1	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
GGT1	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
ID2	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	IGFBP3	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	IL3RA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	EIF3E	psi-mi:“MI:0915”(physical association)	0.560
LUM	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	MAP3K9	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	NDUFV1	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	OXA1L	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	MAPK11	psi-mi:“MI:0915”(physical association)	0.560
PROS1	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	RPL35A	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	SDHC	psi-mi:“MI:0915”(physical association)	0.560
SET	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
SOX10	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	SP2	psi-mi:“MI:0915”(physical association)	0.560
	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	TCF4	psi-mi:“MI:0915”(physical association)	0.560
UNG	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
PRKCA	ZSCAN9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (397): RBCK1 (Affinity Capture-Western), PRKCA (Biochemical Activity), PRKCA (Biochemical Activity), PRKCA (Affinity Capture-RNA), PRKCA (Affinity Capture-RNA), EP300 (Biochemical Activity), PPARG (Affinity Capture-Western), PPARG (Two-hybrid), PRKCA (Affinity Capture-MS), PRKCA (Two-hybrid), EIF2S1 (Biochemical Activity), PRKCA (Affinity Capture-MS), PRKCA (Affinity Capture-MS), PRKCA (Affinity Capture-MS), PRKCA (Affinity Capture-MS)

ESM2 similar proteins: A0A075F932, A8KBH6, F1LM93, K8FE10, O08625, O08835, P04409, P05126, P05130, P05696, P05771, P05772, P10102, P13217, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P25455, P29101, P34693, P40749, P41823, P46096, P46097, P47191, P47861, P48018, P50232, P68403, P68404, P70169, P70610, P90980, Q14184, Q5FWL4

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

200 interactions.

A	Effect	B	Mechanism
1,2-diacyl-sn-glycerol	up-regulates	PRKCA	binding
PRKCA	“up-regulates activity”	HSPB8	phosphorylation
PRKCA	down-regulates	GSK3A	phosphorylation
PRKCA	unknown	EIF6	phosphorylation
PRKCA	down-regulates	GJA1	phosphorylation
PRKCA	down-regulates	HRH1	phosphorylation
PRKCA	down-regulates	ITGB4	phosphorylation
PDPK1	up-regulates	PRKCA	phosphorylation
PRKCA	up-regulates	THOC5	phosphorylation
PRKCA	down-regulates	PTPN6	phosphorylation
PRKCA	up-regulates	LRP1	phosphorylation
PRKCA	up-regulates	PRKCA	phosphorylation
PRKCA	up-regulates	IQGAP1	phosphorylation
PRKCA	up-regulates	CHAT	phosphorylation
PRKCA	down-regulates	TRPC3	phosphorylation
PRKCA	up-regulates	TRPM4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

70 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

6980 predictions. Top by Δscore:

Variant	Effect	Δscore
17:66303024:GGTA:G	donor_loss	1.0000
17:66303025:G:GG	donor_gain	1.0000
17:66303025:G:T	donor_loss	1.0000
17:66304798:GGA:G	donor_gain	1.0000
17:66304799:GAG:G	donor_gain	1.0000
17:66306094:A:AG	acceptor_gain	1.0000
17:66306094:AGG:A	acceptor_gain	1.0000
17:66306094:AGGG:A	acceptor_gain	1.0000
17:66306094:AGGGG:A	acceptor_gain	1.0000
17:66306095:G:GG	acceptor_gain	1.0000
17:66306095:GGG:G	acceptor_gain	1.0000
17:66306095:GGGG:G	acceptor_gain	1.0000
17:66306095:GGGGG:G	acceptor_gain	1.0000
17:66306128:G:T	donor_loss	1.0000
17:66306129:T:A	donor_loss	1.0000
17:66339919:G:GT	donor_gain	1.0000
17:66363215:GT:G	donor_gain	1.0000
17:66415600:A:G	acceptor_gain	1.0000
17:66421198:GAAGA:G	donor_gain	1.0000
17:66496199:A:AG	acceptor_gain	1.0000
17:66496200:G:GA	acceptor_gain	1.0000
17:66496200:GTTT:G	acceptor_gain	1.0000
17:66496281:GAT:G	donor_gain	1.0000
17:66496284:G:GG	donor_gain	1.0000
17:66513316:T:G	acceptor_gain	1.0000
17:66641462:TGACA:T	donor_gain	1.0000
17:66641463:GACA:G	donor_gain	1.0000
17:66641463:GACAG:G	donor_gain	1.0000
17:66641464:ACAG:A	donor_loss	1.0000
17:66641465:CA:C	donor_gain	1.0000

AlphaMissense

4513 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:66302915:C:A	R22S	1.000
17:66302932:G:C	R27S	1.000
17:66302932:G:T	R27S	1.000
17:66302960:C:G	H37D	1.000
17:66302967:T:C	F39S	1.000
17:66302996:T:C	F49L	1.000
17:66302998:C:A	F49L	1.000
17:66302998:C:G	F49L	1.000
17:66302999:T:A	C50S	1.000
17:66302999:T:C	C50R	1.000
17:66303000:G:A	C50Y	1.000
17:66303000:G:C	C50S	1.000
17:66303000:G:T	C50F	1.000
17:66303001:C:G	C50W	1.000
17:66303005:C:G	H52D	1.000
17:66303008:T:A	C53S	1.000
17:66303008:T:C	C53R	1.000
17:66303009:G:A	C53Y	1.000
17:66303009:G:C	C53S	1.000
17:66303009:G:T	C53F	1.000
17:66303010:C:G	C53W	1.000
17:66303017:T:C	F56L	1.000
17:66303018:T:C	F56S	1.000
17:66303018:T:G	F56C	1.000
17:66303019:C:A	F56L	1.000
17:66303019:C:G	F56L	1.000
17:66303023:T:A	W58R	1.000
17:66303023:T:C	W58R	1.000
17:66306097:G:A	G59R	1.000
17:66306097:G:C	G59R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000168 (17:66417420 T>C), RS1000013270 (17:66790654 G>A,T), RS1000016959 (17:66724295 C>A,G), RS1000039814 (17:66462528 T>C), RS1000043758 (17:66614693 T>A), RS1000045436 (17:66525259 T>A), RS1000049939 (17:66706831 A>G), RS1000052018 (17:66775689 T>C), RS1000057170 (17:66474328 A>G,T), RS1000059253 (17:66411668 G>A), RS1000063383 (17:66762937 T>C), RS1000068102 (17:66368761 T>C), RS1000075093 (17:66428662 C>T), RS1000079403 (17:66370784 A>G), RS1000084049 (17:66321557 T>A)

Disease associations

OMIM: gene MIM:176960 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

53 associations (top):

Study	Trait	p-value
GCST001290_2	Height	3.000000e-08
GCST001356_34	Gout	1.000000e-07
GCST002037_19	Post-traumatic stress disorder (asjusted for relatedness)	5.000000e-06
GCST002097_32	Coronary artery calcification	3.000000e-06
GCST002500_20	QT interval	3.000000e-14
GCST002579_25	Heschl’s gyrus morphology	2.000000e-06
GCST003489_4	Food addiction	6.000000e-08
GCST003489_8	Food addiction	6.000000e-07
GCST003598_36	QRS duration	1.000000e-08
GCST003598_9	QRS duration	1.000000e-10
GCST003844_39	QRS duration	2.000000e-11
GCST003870_7	QRS complex (Sokolow-Lyon)	3.000000e-12
GCST003872_21	QRS complex (12-leadsum)	5.000000e-11
GCST003963_1	Possible neuropathic pain in post total joint replacement surgery for osteoarthritis	4.000000e-06
GCST005171_54	QT interval	7.000000e-14
GCST005232_21	Neuroticism	7.000000e-07
GCST006057_1	Percent glycated albumin	4.000000e-09
GCST006058_3	Total glycated albumin levels	6.000000e-07
GCST006945_6	Feeling guilty	5.000000e-09
GCST007103_25	QRS duration	8.000000e-19
GCST007104_25	QRS duration	1.000000e-37
GCST008103_165	Bipolar disorder	7.000000e-06
GCST008142_5	Systolic blood pressure	7.000000e-06
GCST009187_10	Lateral occipital cortex volume	7.000000e-06
GCST009861_1	Cryptosporidiosis	4.000000e-08
GCST010151_29	Carotid intima media thickness x smoking interaction	2.000000e-06
GCST010320_71	PR interval	3.000000e-07
GCST010321_58	PR interval	3.000000e-09
GCST010573_4	Cardiorespiratory fitness (800m run time)	4.000000e-08
GCST010796_1147	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-28

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004682	QT interval
EFO:0007829	eating behaviour
EFO:0007830	food addiction measurement
EFO:0005054	QRS complex
EFO:0007742	QRS amplitude
EFO:0005762	neuropathic pain
EFO:0007660	neuroticism measurement
EFO:0009304	percent glycated albumin
EFO:0009305	total glycated albumin
EFO:0009595	guilt measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004462	PR interval
EFO:0004328	exercise test
EFO:0004327	electrocardiography
EFO:0007828	daytime rest measurement
EFO:0007800	body fat percentage
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093867 (PROTEIN FAMILY), CHEMBL2096620 (PROTEIN FAMILY), CHEMBL299 (SINGLE PROTEIN), CHEMBL3137267 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 386,240 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1863513	INGENOL MEBUTATE	4	1,475
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL535	SUNITINIB	4	79,020
CHEMBL265502	SURAMIN	3	36,848
CHEMBL38380	FASUDIL	3	11,953
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2107337	ENZASTAURIN HYDROCHLORIDE	3	516
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL279115	PHORBOL MYRISTATE ACETATE	2	1,362
CHEMBL28509	EDELFOSINE	2
CHEMBL3137336	UPROSERTIB	2
CHEMBL574737	UCN-01	2
CHEMBL1922094	APITOLISIB	2
CHEMBL1944698	ZOTIRACICLIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL3545396	BMS-690514	2
CHEMBL3982723	DAROVASERTIB	2
CHEMBL444478	ACETOSIDE	2
CHEMBL449158	BRYOSTATIN 1	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs16960228	Efficacy	3	hydrochlorothiazide	Hypertension
rs4791040	Efficacy	3	hydrochlorothiazide	Hypertension
rs9381299	Toxicity	3	bevacizumab	Hypertension

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4791040	PRKCA	3	0.00	1	hydrochlorothiazide
rs16960228	PRKCA	3	0.00	1	hydrochlorothiazide
rs9909004	PRKCA		0.00	0
rs9303504	PRKCA		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Delta subfamily

Most potent curated ligand interactions (14 total), top 14:

Ligand	Action	Affinity	Parameter
ingenol mebutate	Activation	9.52	pKi
darovasertib	Inhibition	8.72	pIC50
sotrastaurin	Inhibition	8.68	pIC50
Gö 6976	Inhibition	8.64	pIC50
10-Me-Aplog-1	Activation	8.33	pKi
Gö 6983	Inhibition	8.15	pIC50
Ro-32-0432	Inhibition	8.05	pIC50
RasGRP activator 1	Binding	7.79	pKi
GF109203X	Inhibition	7.7	pIC50
7-hydroxystaurosporine	Inhibition	7.54	pIC50
balanol	Inhibition	7.52	pIC50
ruboxistaurin	Inhibition	6.44	pIC50
enzastaurin	Inhibition	6.1	pIC50
forsythiaside	Inhibition	5.72	pIC50

Binding affinities (BindingDB)

229 measured of 296 human assays (301 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4442196	IC50	0.09 nM
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(2-fluorophenyl)pyrazine-2-carboxamide	IC50	0.1 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[2-morpholin-4-yl-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-morpholin-4-ylphenyl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-(3,6-dihydro-2H-pyran-4-yl)-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(2-morpholin-4-ylquinazolin-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[2-(trifluoromethyl)-1H-indol-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(dimethylamino)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-(4,4-difluoropiperidin-1-yl)-5-fluoropyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1-methylindol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indazol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(6-fluoro-2-morpholin-4-ylquinazolin-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(2-methyl-1H-indol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indol-4-yl)pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[3-morpholin-4-yl-5-(trifluoromethyl)phenyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[4-amino-4-(hydroxymethyl)piperidin-1-yl]-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.13 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL3741746	IC50	0.13 nM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(5-fluoro-2-morpholin-4-ylpyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.14 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4528495	IC50	0.15 nM
3-amino-N-[3-[4-amino-4-(ethoxymethyl)piperidin-1-yl]-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.16 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[5-morpholin-4-yl-2-(trifluoromethyl)phenyl]pyrazine-2-carboxamide	IC50	0.17 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4538431	IC50	0.17 nM
CHEMBL4443190	IC50	0.18 nM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(6-morpholin-4-yl-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.19 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(azetidin-1-yl)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-phenylpyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-(4-methoxyphenyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-6-(2-fluorophenyl)-N-(4-piperazin-1-yl-3-pyridinyl)pyrazine-2-carboxamide	IC50	0.2 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4435580	IC50	0.22 nM
3-amino-N-[3-[(1S,5R,8S)-8-amino-6-oxa-3-azabicyclo[3.2.1]octan-3-yl]-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.24 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[(3S,4R)-4-amino-3-fluoropiperidin-1-yl]-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.25 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-[4-amino-4-(hydroxymethyl)piperidin-1-yl]-2-pyridinyl]-6-(1-morpholin-4-ylisoquinolin-3-yl)pyrazine-2-carboxamide	IC50	0.25 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-[[(2R)-1-hydroxypropan-2-yl]amino]-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.26 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1-methylpyrazolo[3,4-d]pyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.27 nM	US-9452998: Protein kinase C inhibitors and methods of their use
NSC_4179	KI	0.27 nM
Butyric acid (1aS,1bS,4aS,7aS,8R,9S,9aR)-9-butyryloxy-4a,7b-dihydroxy-3-((R)-hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl ester	KD	0.28 nM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(2-morpholin-4-ylpyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.29 nM	US-9452998: Protein kinase C inhibitors and methods of their use
NSC_6437389	KI	0.29 nM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[2-morpholin-4-yl-5-(trifluoromethyl)pyrimidin-4-yl]pyrazine-2-carboxamide	IC50	0.3 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-3-fluoropiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.3 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-[(3S)-3-methylmorpholin-4-yl]-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.32 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.33 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-fluoro-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.33 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-6-(2-amino-5-chloropyrimidin-4-yl)-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.35 nM	US-9452998: Protein kinase C inhibitors and methods of their use
NSC_105100	KI	0.35 nM
3-amino-N-[3-(4-amino-3-methoxypiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.36 nM	US-9452998: Protein kinase C inhibitors and methods of their use
CHEMBL4587471	IC50	0.36 nM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[6-cyclopropyl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(3-cyano-2-pyridinyl)pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-(2-carbamoyl-5-fluoropyrimidin-4-yl)pyrazine-2-carboxamide	IC50	0.4 nM	US-9452998: Protein kinase C inhibitors and methods of their use

ChEMBL bioactivities

1518 potent at pChembl≥5 of 1728 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	STAUROSPORINE
10.05	IC50	0.09	nM	CHEMBL4442196
9.89	IC50	0.13	nM	CHEMBL3892099
9.89	IC50	0.13	nM	CHEMBL3984070
9.89	IC50	0.13	nM	CHEMBL3932204
9.89	IC50	0.13	nM	CHEMBL3958761
9.89	IC50	0.13	nM	CHEMBL3984009
9.89	IC50	0.13	nM	CHEMBL3951893
9.89	IC50	0.13	nM	CHEMBL3980746
9.89	IC50	0.13	nM	CHEMBL3943147
9.89	IC50	0.13	nM	CHEMBL3970090
9.89	IC50	0.13	nM	CHEMBL3983009
9.89	IC50	0.13	nM	CHEMBL3957715
9.89	IC50	0.13	nM	CHEMBL3958917
9.89	IC50	0.13	nM	CHEMBL3969856
9.89	IC50	0.13	nM	CHEMBL3966643
9.89	IC50	0.13	nM	CHEMBL3982497
9.89	IC50	0.13	nM	CHEMBL3966595
9.89	IC50	0.13	nM	CHEMBL3893533
9.89	IC50	0.13	nM	CHEMBL3920517
9.89	IC50	0.13	nM	CHEMBL3895998
9.89	IC50	0.13	nM	CHEMBL3963605
9.89	IC50	0.13	nM	CHEMBL3741746
9.85	IC50	0.14	nM	CHEMBL3945647
9.85	IC50	0.14	nM	CHEMBL4575056
9.85	Ki	0.14	nM	CHEMBL46094
9.82	IC50	0.15	nM	CHEMBL3943813
9.82	IC50	0.15	nM	CHEMBL4528495
9.80	IC50	0.16	nM	CHEMBL3987185
9.77	IC50	0.17	nM	CHEMBL3970893
9.77	IC50	0.17	nM	CHEMBL4538431
9.74	IC50	0.18	nM	CHEMBL4443190
9.72	IC50	0.19	nM	CHEMBL3976541
9.72	IC50	0.19	nM	CHEMBL3942619
9.72	EC50	0.19	nM	CHEMBL3741746
9.70	IC50	0.2	nM	CHEMBL3932204
9.70	IC50	0.2	nM	CHEMBL3957149
9.70	IC50	0.2	nM	CHEMBL3946659
9.70	IC50	0.2	nM	CHEMBL5592487
9.70	Ki	0.2	nM	CHEMBL27768
9.66	IC50	0.22	nM	CHEMBL3901073
9.66	IC50	0.22	nM	CHEMBL4435580
9.62	IC50	0.24	nM	CHEMBL4115475
9.60	IC50	0.25	nM	CHEMBL3915489
9.60	IC50	0.25	nM	CHEMBL3960459
9.60	IC50	0.25	nM	CHEMBL3912038
9.59	Ki	0.26	nM	DEBROMOAPLYSIATOXIN
9.59	IC50	0.26	nM	CHEMBL4109540
9.57	IC50	0.27	nM	CHEMBL3967547
9.55	Kd	0.28	nM	CHEMBL27768

PubChem BioAssay actives

1209 with measured affinity, of 4336 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(dimethylamino)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-morpholin-4-yl-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-morpholin-4-ylisoquinolin-1-yl)pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indol-4-yl)pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(1H-indazol-4-yl)pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-22-acetyloxy-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] naphthalene-2-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,25R)-12-benzoyloxy-10,11-dihydroxy-9-(hydroxymethyl)-13,15-dimethyl-22-oxo-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0001	uM
3-amino-N-[4-(4-aminopiperidin-1-yl)-3-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0001	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	165147: Inhibition Protein kinase C (PKC)	ic50	0.0001	uM
3-amino-N-[3-(4-amino-3-fluoropiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0002	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[6-(azetidin-1-yl)-3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-nitrobenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-12-benzoyloxy-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-propan-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-2-yl]methyl benzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] 4-methoxybenzoate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0002	uM
3-amino-N-[4-[(3S,4S)-4-amino-3-methoxypiperidin-1-yl]-3-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0002	uM
[(1S,2S,6R,10S,11R,13S,14R,15R)-13-butanoyloxy-1,6-dihydroxy-8-(hydroxymethyl)-4,12,12,15-tetramethyl-5-oxo-14-tetracyclo[8.5.0.02,6.011,13]pentadeca-3,8-dienyl] butanoate	164151: Binding Affinity against protein kinase C alpha	ki	0.0002	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-(3-fluoro-2-pyridinyl)pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0003	uM
3-amino-N-[3-(4-amino-3-methoxypiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0003	uM
N-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-8-yl]-N’-[(2S,5S)-5-(hydroxymethyl)-1-methyl-3-oxo-2-propan-2-yl-2,4,5,6-tetrahydro-1,4-benzodiazocin-9-yl]tetradecanediamide	162867: Binding affinity for human Protein kinase C alpha with [Ca2+]	kd	0.0003	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S,5S)-5-(3-hydroxyphenyl)-5-methoxypentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	687829: Inhibition of [3H]PDBu binding to PKCalpha C1A domain	ki	0.0003	uM
[(1R,2S,4R,5R,6S,7S,9R,10S,11S,12S,13S,14S,15R,22R,25R)-2-(benzoyloxymethyl)-10,11,22-trihydroxy-9-(hydroxymethyl)-13,15-dimethyl-4-prop-1-en-2-yl-8,24,26,27-tetraoxaheptacyclo[12.10.1.14,23.15,23.01,6.07,9.011,25]heptacosan-12-yl] pyridine-4-carboxylate	1576882: Agonist activity at Protein kinase C in human MT4 cells infected with HIV-1 NL4-3 assessed as inhibition of viral replication measured on day 3 post-infection by Nano-Glo luciferase assay	ic50	0.0004	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-4-pyridinyl]-6-[3-(trifluoromethoxy)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0004	uM
(1S,3R,4S,5S,9R,13S,14R)-3-[(2S,5S)-5-(2-bromo-5-hydroxyphenyl)-5-methoxypentan-2-yl]-13-hydroxy-9-[(1R)-1-hydroxyethyl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	517262: Inhibition of [3H]PDBu binding to PKC alpha C1A peptide	ki	0.0004	uM
3-(7-methyl-1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0004	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437217: Inhibition of PKCalpha (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0005	uM
3-[2-chloro-7-(methylaminomethyl)naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437217: Inhibition of PKCalpha (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0005	uM
3-(1H-indol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0005	uM
(10S,13S)-13-(hydroxymethyl)-9-methyl-5-octyl-10-propan-2-yl-3,9,12-triazatricyclo[6.6.1.04,15]pentadeca-1,4,6,8(15)-tetraen-11-one	163026: Displacement of [3H]- PDBu from recombinant PKC alpha expressed in baculovirus	ki	0.0005	uM
[(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,21R,23R,25S)-25-acetyloxy-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] (2E,4E)-octa-2,4-dienoate	1228109: Inhibition of [20-3H]phorbol 12,13-dibutyrate binding to human PKCalpha by scintillation counting based poly(ethylene) glycol precipitation assay	ki	0.0005	uM
3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0008	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-thieno[2,3-d]pyrimidin-4-ylpyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0008	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)naphthalen-1-yl]pyrrole-2,5-dione	1799253: Protein Kinase Assays from Article 10.1021/jm901108b: “Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes.”	ic50	0.0009	uM
3-[6-fluoro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0010	uM
3-[2-chloro-7-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione	1437230: Reversible competitive inhibition of PKCalpha (unknown origin)	ki	0.0010	uM
(3Z)-3-[[5-(2-nitrophenyl)-1H-pyrazol-4-yl]methylidene]-1H-indol-2-one	739586: Inhibition of PKC alpha (unknown origin) using PIP2 as substrate after 1 hr by Kinase-Glo assay	ic50	0.0010	uM
(1S,3R,4S,5S,9R,13S,14R)-13-hydroxy-9-[(1R)-1-hydroxyethyl]-3-[(2S)-5-(3-hydroxyphenyl)pentan-2-yl]-4,14,16,16-tetramethyl-2,6,10,17-tetraoxatricyclo[11.3.1.11,5]octadecane-7,11-dione	768066: Displacement of [3H]PDBu from PKCalpha C1A domain (unknown origin)	ki	0.0010	uM
[(1S)-2-hydroxy-1-[(4E)-4-nonylidene-5-oxooxolan-2-yl]ethyl] nonanoate	163171: Affinity for protein kinase C alpha	ki	0.0012	uM
3-(1H-indol-3-yl)-4-[3-(4-methylpiperazin-1-yl)isoquinolin-1-yl]pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0014	uM
[(2R,4Z)-2-(hydroxymethyl)-4-[5-methyl-3-(2-methylpropyl)hexylidene]-5-oxooxolan-2-yl]methyl 2,2-dimethylpropanoate	261779: Displacement of [20-3H]PDBu from recombinant PKC alpha in presence of phosphatidylserine	ki	0.0014	uM
3-(1-methylindol-3-yl)-4-(2-piperazin-1-ylquinazolin-4-yl)pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0014	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149076: Binding affinity to human PRKCA incubated for 45 mins by Kinobead based pull down assay	kd	0.0015	uM
[(1S,3S,5Z,7R,8E,11R,13E,15S,17R,21R,23R,25S)-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-25-yl] 2,2-dimethylpropanoate	400689: Displacement of [3H]PDBu form PKCalpha	ki	0.0016	uM
3-[6-chloro-2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	689998: Inhibition of PKCalpha by scintillation proximity assay	ic50	0.0017	uM
(15R,16R,18S)-16-(hydroxymethyl)-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaene-3,5-dione	155717: In vitro inhibition of protein kinase C (PKC)	ic50	0.0017	uM
3-[2-chloro-6-[(dimethylamino)methyl]naphthalen-1-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	1437217: Inhibition of PKCalpha (unknown origin) after 60 mins in presence of [gamma33P]ATP by scintillation proximity assay	ic50	0.0018	uM
[(1S)-2-hydroxy-1-[(4Z)-4-nonylidene-5-oxooxolan-2-yl]ethyl] nonanoate	163171: Affinity for protein kinase C alpha	ki	0.0018	uM
3-amino-N-[3-(4-amino-4-methylpiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	1768632: Inhibition of PKC-alpha (unknown origin)	ic50	0.0019	uM
3-amino-N-[3-(4-aminopiperidin-1-yl)-2-pyridinyl]-6-[3-(trifluoromethyl)-2-pyridinyl]pyrazine-2-carboxamide	2098472: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method	ic50	0.0020	uM

CTD chemical–gene interactions

154 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	decreases reaction, increases activity, increases abundance, increases localization, increases expression (+6 more)	22
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	11
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	8
Tetrachlorodibenzodioxin	decreases reaction, increases activity, affects cotreatment, decreases expression, affects activity (+3 more)	5
Go 6976	affects localization, decreases reaction, decreases phosphorylation, increases reaction, decreases activity (+1 more)	4
Resveratrol	affects reaction, decreases reaction, increases activity, increases localization, increases phosphorylation (+1 more)	4
Cisplatin	decreases expression, increases reaction, increases metabolic processing, increases phosphorylation, decreases response to substance	4
bisphenol A	decreases methylation, increases phosphorylation, affects cotreatment, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases reaction, decreases expression, increases expression, affects binding	3
Acetaminophen	decreases expression, increases expression	3
Curcumin	decreases expression, affects reaction, increases expression, increases activity, increases phosphorylation (+1 more)	3
Estradiol	decreases expression, decreases activity, increases expression, increases phosphorylation, decreases reaction (+1 more)	3
Smoke	affects localization, increases activity, decreases expression, increases expression	3
Tretinoin	increases phosphorylation, affects reaction, increases activity, increases expression	3
naringenin	affects cotreatment, increases expression, affects localization, decreases reaction	2
lead acetate	increases phosphorylation, affects localization, decreases reaction, increases activity, decreases expression	2
cobaltous chloride	decreases expression	2
calphostin C	decreases reaction, increases activity	2
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	increases expression, affects localization, decreases reaction	2
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	affects localization, decreases reaction, increases activity	2
entinostat	increases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression, increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	increases phosphorylation	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Diethylhexyl Phthalate	decreases expression, decreases reaction, affects reaction, increases expression	2
Doxorubicin	affects cotreatment, increases phosphorylation, increases transport, affects reaction, affects response to substance (+1 more)	2
Hydrogen Peroxide	affects expression, increases phosphorylation	2
Metformin	affects cotreatment, decreases expression, decreases reaction, increases phosphorylation	2

ChEMBL screening assays

1148 unique, capped per target: 1131 binding, 15 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000235	Binding	Activation of PKC in PMA-stimulated human LNCAP cells assessed as ERK phosphorylation at 1 nM to 10 uM by Western blot relative to PMA	Conformationally constrained analogues of diacylglycerol (DAG). 31. Modulation of the biological properties of diacylgycerol lactones (DAG-lactones) containing rigid-rod acyl groups separated from the core lactone by spacer units of different lengths. — J Med Chem
CHEMBL688555	Functional	Retained protein kinase C activity in the presence of 1.25 uM compound	Synthesis and biological activity of novel quaternary ammonium derivatives of alkylglycerols as potent inhibitors of protein kinase C. — J Med Chem
CHEMBL4424903	ADMET	Inhibition of human full-length N-terminal His6-tagged PKCalpha expressed in baculovirus infected Sf21 insect cells using Histone H1 as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8N4	Abcam HCT 116 PRKCA KO	Cancer cell line	Male
CVCL_B9AP	Abcam MCF-7 PRKCA KO	Cancer cell line	Female
CVCL_B9QD	Abcam A-549 PRKCA KO	Cancer cell line	Male
CVCL_D1U2	Abcam U-87MG PRKCA KO	Cancer cell line	Male
CVCL_D9PK	Ubigene HEK293 PRKCA KO	Transformed cell line	Female
CVCL_KT93	HeLa SilenciX PKCalpha	Cancer cell line	Female
CVCL_TG80	HAP1 PRKCA (-) 1	Cancer cell line	Male
CVCL_TG81	HAP1 PRKCA (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.